Talk:Human Physiology/The Immune System

Corrections I did some more changes on the organs and tissues of the lymph system. I am glad someone added the extra material.. it is good. I love the way the chapter is shaping up. I added something about vitiligo and hay fever. And made some bullets. I am still concerned about the outline that is still there - about bacteria, etc. Should we just delete it? Ann

Lymph system move
I moved the section about the lymph system from the cardiovascular chapter to this one- I just put it in and I think it probably does some repeating- feel free to delete or change it- We just felt that it made more sense in this chapter rather than in cardiovascular Stephanie greenwood 17:24, 19 March 2007 (UTC)

Adaptive Defense
The section on adaptive defense definitely needs some work. I spent a lot of time on it, but it needs a lot more organization. If I don't get to it, will someone please take a look at it? --Shaleneroberts 01:58, 18 March 2007 (UTC)

We have two sections on T cells... can we combine them? It looks like the 2nd section is cut from wikipedia or something. I don't really understand it very well. Please feel free to reorganize things however you see fit!never2late 02:24, 18 March 2007 (UTC)

Hi guys I hope I am not messing up what you got going I just thought the things I added were important enough to go into the chapter if we need to move them somewhere else I am fine with that. --User:Shellybird2

I just added a section on organs - kind of anatomy... but thought it was useful. Please feel free to move things around or remove parts of the outline we don't need. It is looking good!!!! I like all new stuff!!!!!! never2late 05:24, 18 March 2007 (UTC)

Suggested T cell revision
Here is what the T cell sections currently look like, along with some suggested revisions. If you want to comment on these changes--reasons for or against, please do so.

Different Types of T Lymphocyte Cells
I HAVE DELETED THE BELOW THAT NEEDED TO BE DELETED, WORKING ON REWRITING STUFF.--Shaleneroberts 17:12, 19 March 2007 (UTC) Several different subsets of T cells have been described, each with a distinct function.

Cytotoxic T cells (Tc cells) destroy virally infected cells and tumor cells, and are also implicated in transplant rejection. These cells are also known as CD8+ T cells, since they express the CD8 glycoprotein at their surface.
 * I like that there is an explanation for why they are called CD8+, and in the next paragraph why Th cells are also called CD4+. I will probably refer to Tc and Th cells rather than CD8+ and CD4+ in lecture, but I would like to keep these explanations in anyway. Especially when reading about HIV you commonly hear about CD4+ cells.

Helper T cells, (Th cells) are the "middlemen" of the adaptive immune system. Once activated, they divide rapidly and secrete small proteins called cytokines that regulate or "help" the immune response. These cells (also called CD4+ T cells) are a target of HIV infection; the virus infects the cell by using the CD4 protein to gain entry. The loss of Th cells as a result of HIV infection leads to the symptoms of AIDS.

Memory T cells are a subset of antigen-specific T cells that persist long-term after an infection has resolved. They quickly expand to large numbers of effector T cells upon re-exposure to their cognate antigen, thus providing the immune system with "memory" against past infections. [Memory T cells comprise two subtypes: central memory T cells (TCM cells) and effector memory T cells (TEM cells).] Memory cells may be either CD4+ or CD8+.
 * I would probably delete the second to last sentence [I put brackets around it], just because I don't plan on distinguishing between TCM and TEM cells.

Regulatory T cells (Treg cells), formerly known as suppressor T cells, are crucial for the maintenance of immunological tolerance. Their major role is to shut down T cell mediated immunity towards the end of an immune reaction and to suppress auto-reactive T cells that escaped the process of negative selection in the thymus. [Two major classes of regulatory T cells have been described, including the naturally occurring Treg cells and the adaptive Treg cells. Naturally occurring Treg cells (also known as CD4+CD25+FoxP3+ Treg cells) arise in the thymus, whereas the adaptive Treg cells (also known as Tr1 cells or Th3 cells) may originate during a normal immune response. Naturally occurring Treg cells can be distinguished from other T cells by the presence of an intracellular molecule called FoxP3. Mutations of the FOXP3 gene can prevent regulatory T cell development, causing the fatal autoimmune disease IPEX.]
 * I would delete all info within brackets, just because I think it is beyond the scope of our class. It would be nice if the first part of the paragraph could be explained in simpler terms (or maybe just a slightly longer explanation would help).

Natural Killer T cells (NKT cells) are a special kind of lymphocyte that bridges the adaptive immune system with the innate immune system. Unlike conventional T cells that recognize peptide antigen presented by major histocompatibility complex (MHC) molecules, NKT cells recognize glycolipid antigen presented by a molecule called CD1d. Once activated, these cells can perform functions ascribed to both Th and Tc cells (i.e. cytokine production and release of cytolytic/cell killing molecules).
 * I would end here, try to give a bit simpler explanation of NKT cells, and delete the following.

γδ T cells represent a small subset of T cells that possess a distinct TCR on their surface. A majority of T cells have a TCR composed of two glycoprotein chains called α- and β- TCR chains. However, in γδ T cells, the TCR is made up of one γ-chain and one δ-chain. This group of T cells is much less common (5% of total T cells) than the αβ T cells, but are found at their highest abundance in the gut mucosa, within a population of lymphocytes known as intraepithelial lymphocytes (IELs). The antigenic molecules that activate γδ T cells are still widely unknown. However, γδ T cells are not MHC restricted and seem to be able to recognise whole proteins rather than requiring peptides to be presented by MHC molecules on antigen presenting cells. Some recognize MHC class IB molecules though. Human Vγ9/Vδ2 T cells, which constitute the major γδ T cell population in peripheral blood, are unique in that they specifically and rapidly respond to a small non-peptidic microbial metabolite, HMB-PP, an isopentenyl pyrophosphate precursor.

THE FUNCTIONS OF T LYMPHOCYTES
T lymphocytes cells help with all components of the immune system, including cell elemination by killer T cells and maintaining roles by helper and suppressor T cells. Although the specific mechanisms of activation vary slightly between different types of T cells, the "two-signal model" in CD4+ T cells holds true for most. [Activation of CD4+ T cells occurs through the engagement of both the T cell receptor and CD28 on the T cell by the Major histocompatibility complex peptide and B7 family members on the APC respectively. Both are required for production of an effective immune response; in the absence of CD28 co-stimulation, T cell receptor signalling alone results in anergy. The signalling pathways downstream from both CD28 and the T cell receptor involve many proteins.]
 * Starting with the info in brackets, and continuing down to the next several paragraphs: This is good information and nicely written, but largely goes beyond the scope of our class. I would delete all of it and give a simpler explanation of what T cells do--their role in fighting viruses and cancer, for instance.

The first signal is provided by binding of the T cell receptor to a short peptide presented by the major histocompatibility complex (MHC) on another cell. This ensures that only a T cell with a TCR specific to that peptide is activated. The partner cell is usually a professional antigen presenting cell (APC), usually a dendritic cell in the case of naïve responses, although B cells and macrophages can be important APCs. The peptides presented to CD8+ T cells by MHC class I molecules are 8-9 amino acids in length; the peptides presented to CD4+ cells by MHC class II molecules are longer, as the ends of the binding cleft of the MHC class II molecule are open.

The second signal comes from co-stimulation, in which surface receptors on the APC are induced by a relatively small number of stimuli, usually products of pathogens, but sometimes breakdown products of cells, such as necrotic-bodies or heat-shock proteins. The only co-stimulatory receptor expressed constitutively by naïve T cells is CD28, so co-stimulation for these cells comes from the CD80 and CD86 proteins on the APC. Other receptors are expressed upon activation of the T cell, such as OX40 and ICOS, but these largely depend upon CD28 for their expression. The second signal licenses the T cell to respond to an antigen. Without it, the T cell becomes anergic and it becomes more difficult for it to activate in future. This mechanism prevents inappropriate responses to self, as self-peptides will not usually be presented with suitable co-stimulation.

The T cell receptor exists as a complex of several proteins. The actual T cell receptor is composed of two separate peptide chains which are produced from the independent T cell receptor alpha and beta (TCRα and TCRβ) genes. The other proteins in the complex are the CD3 proteins; CD3εγ and CD3εδ heterodimers and most importantly a CD3ζ homodimer which has a total of six ITAM motifs. The ITAM motifs on the CD3ζ can be phosphorylated by Lck and in turn recruit ZAP-70. Lck and/or ZAP-70 can also phosphorylate the tyrosines on many other molecules, not least CD28, Trim, LAT and SLP-76, which allows the aggregation of signalling complexes around these proteins.

Phosphorylated LAT recruits SLP-76 to the membrane, where it can then bring in PLCγ, VAV1, Itk and potentially PI3K. Both PLCγ and PI3K which act on PI(4,5)P2 on the inner leaflet of the membrane to create the active intermediaries di-acyl glycerol (DAG), inositol-1,4,5-trisphosphate (IP3) and phosphatidlyinositol-3,4,5-trisphosphate (PIP3). DAG binds and activates some PKCs, most importantly in T cells PKCθ, which is important for activating the transcription factors NF-κB and AP-1. IP3 is released from the membrane by PLCγ and diffuses rapidly to activate receptors on the ER which induce the release of calcium. The released calcium then activates calcineurin, and calcineurin activates NFAT, which then translocates to the nucleus.
 * Those are my suggestions. I'm going to leave it up to you (the students) to actually make the revisions. You don't have to agree with me--you can change the information more or less than this. This chapter is looking great! Provophys 15:21, 19 March 2007 (UTC)

TAKE YOUR CAPS LOCK OFF
Or put it on, but it looks bad when some subheadings are ALL CAPITAL and others aren't. Consistency is good. I de-capitalized headings in this chapter.